Vaccination is one of the most cost-effective ways of avoiding disease, currently preventing 2-3 million deaths a year. This figure could increase to a further 1.5 million if global coverage of vaccinations improves.

However, the anti-vaccination movement has been growing in recent years. The World Health Organization (WHO) now list it as one of the top 10 potential threats to global health in 2019.

The dangerous implications of this growing vaccine hesitancy can be clearly seen in the Philippines. Earlier this year an outbreak of the highly contagious measles virus infected over 8,000 people. More than 130 of these died, and sadly many of them were children.

This measles outbreak arose in response to complications related to a dengue vaccination, Dengvaxia. Developed by a French drugs manufacturer, the vaccine reportedly offered protection against the potentially fatal mosquito-borne disease, Dengue Fever. In an attempt to mitigate the disease, Philippine authorities provided over 800,000 children with the vaccination in 2016. However, a year later it was revealed that this vaccination could potentially worsen the deadly disease in those who had not previously been exposed to the virus. This side effect unfortunately resulted in 14 deaths.

The immense effect that this scare has had on the country is highlighted by the rapidly decreasing immunisation rate, falling from 75% in 2016 to just 60% in 2017. This decrease makes potentially fatal outbreaks of otherwise preventable diseases ever more likely.

Unfortunately the Philippines is not the only country to experience the negative implications of the anti-vaccination movement first hand. It was recently reported that there has been a measles outbreak in Hackney, London. As a result local parents are being urged to keep their children’s vaccinations up to date.

The increasing frequency of these outbreaks across the world highlights the negative impact that vaccine hesitancy is having on a global scale. Unfortunately more and more lives will be put at risk if the anti-vaccination movement continues to grow at its current rate.

This article is the first in a two part series on the anti-vaccination movement. To read the second installment please click here.

Flu: Are Llamas the Solution?

The annual flu season is upon us and many of us get vaccinated against prevalent strains of influenza, identified from the southern hemisphere’s winter. Flu is caused by a virus that has the ability to mutate quickly, regularly leading to new strains and the possibility of outbreaks each year.

What flu researchers are hoping for is a vaccination that could combat all strains of the virus, to reduce, or even eliminate, the need for yearly vaccinations. Up until now, such a solution has proved elusive, but recent research published in Science suggests the answer could lie with llamas!

Whilst humans produce large antibodies that attack flu antigens directly, llamas produce much smaller antibodies that target harder to reach areas of the virus. Areas that don’t mutate regularly.
Researchers at the Scripps Institute in California examined the numerous antibodies present in llama blood, finding four that could potentially fight flu in humans. These four antibodies were effective on all but one of the sixty variations of flu they were tested on.

Yet what’s especially interesting about the research, is its possible application. The research suggests that an effective delivery method could use gene therapy. This would be particularly beneficial for the elderly, as traditional vaccinations become less effective as the efficiency of the immune system declines. The use of gene therapy could mean targeted cells can immediately produce the desired antibodies of their own accord.

Whilst the initial results are encouraging, the study is still ongoing. If upcoming human trials are successful, then the goal of producing a vaccine that would be effective for multiple seasons, might not be so far off. But as research continues, the question remains are we doing enough to protect the most vulnerable in society, from what can be a deadly illness.

Gene editing could eliminate some diseases – but at what cost to the future of the human race? What is the true risk of gene editing?

Originally discovered by a researcher from Osaka University in 1987, gene editing could potentially be used to eliminate heritable diseases through deleting or changing certain coding in embryos. However, the technology involved in this editing is still in the experimental stages, and as such is currently banned in most countries. There is a fear that the changes in DNA could be passed on to future generations, with unpredictable side-effects.

It appears as though these fears are about to be put to the test for the first time in history, as a scientist in China has recently claimed to have produced the world’s first genetically-edited babies. This is yet to be verified, however, if confirmed it could have immense ethical and moral implications.

He Jiankui, a professor from The Southern University of Science and Technology in Shenzhen, is claiming to have edited embryos for seven couples during fertility treatment. According to him, one pregnancy has resulted from this so far.

Jiankui revealed that all of the men in his experiment had HIV while all of the women did not. However, the fathers’ infections are deeply suppressed thanks to standard HIV medicines. Simple methods exist to prevent them from infecting their offspring.

The existence of these treatments mean that the scientist’s intervention was not aimed at preventing HIV transmission. Instead, he hoped to provide the offspring with protection against the disease, reducing their chances of contracting it during their lifetime.

This breakthrough intervention has raised many ethical questions.

Any editing errors within the genes could have potentially fatal effects on the growth of the foetus.

Experts worry that we won’t know the full consequences of this gene editing until we can study future generations of the offspring concerned. Even if the editing works perfectly, people without normal genes may be at a greater risk of contracting other viruses.

Ethical questions have also been raised regarding consent. With the consent forms referring to the experiment as an Aids Vaccine Development Programme it is likely that the participants were not made fully aware of the potential risks of the study.

What is particularly shocking is the fact that Jiankui’s work remained a secret for so long. He did not register the clinical trial with Chinese authorities until November, long after the study had begun.

As a country that has been at the forefront of gene editing for several years, China has failed to update its regulations at the same pace, to reflect the risk of gene editing. A 2003 ‘ethics guidance’ document bans the use of research embryos for reproduction. However, the punishments for violations of this regulation remain unspecified.

While China have declared He Jiankui’s work a violation of their law, the incident serves to highlight a concerning gap in their ethical review processing.

Here at Infonetica we have been developing systems to manage the ethical review process for over ten years. With the ethics debate widening, our Ethics Review Manager (ERM) software can manage the processing of ethical decisions for a wide range of organisations.

It is well accepted that children are not just miniature adults and so ideally should only receive drugs that have been tested in paediatric trials. However, there is also evidence that the difference between male and female patients can be just as important.

Sleeping pill, Ambien, is a good example of a drug that works differently in men and women. The US Food and Drug Administration (FDA) discovered that men metabolize the drug much faster than women. This led to the FDA cutting recommended doses for women by half.

Even the humble aspirin has very different effects on men and women in terms of lowering risk of heart disease.

Findings like these prompted the FDA to release a set of guidelines to the pharmaceutical industry detailing the exceptions for excluding a gender from clinical trials, such as testing a prostate cancer medication or other male or female-specific drug. In theory, women have been included equally in drug studies since 2001.

However, a report in the journal, Cell Metabolism, suggests that there is still a long way to go to eliminate the gender gap in medical trials. According to the report, there is still a tendency to treat the sexes as equivalent, ignoring how fluctuations of sex hormones in experimental settings impact outcomes.

The authors of this article are not alone – an article published in the journal, Cancer, also points to a gender bias in oncology trials – excluding those cancers that only present in a single sex of patient of course.

I have written before about the massive under-representation of ethnic minorities in drug trials and the actions to address this in the US. However, the difference between male and female patients is less widely reported.

Is this, as some article have suggested, because things like periods and menopause make female trial participants a more unpredictable proposition? I certainly hope not.

I suspect is it largely the fact that white, middle-aged men are the easiest (and therefore cheapest) group to recruit. Recruitment is one of the most time-consuming and expensive parts of a drug trial – failure to recruit means the whole trial will collapse.

Trials have a responsibility to investigate a drug’s effect on a sample that is as close to the target market as is practically possible. It means ensuring trials are design to account for the difference between male and female patients.

Doing so will inevitable increase the cost of some trials but if the results are more representative of a drug’s behaviour in the population isn’t it a cost that is worth bearing?

The anti-vaccination movement is a relatively new, largely US phenomenon. It has been roundly criticised in medical circles. However, it stems from a desire (albeit perhaps misguided) of parents to do what’s best for their children.

The anti-vaccination movement has snowballed from one, now totally discredited, paper into an internet full of half-truths and outright lies.

Don’t get me wrong, the internet is a largely immensely positive thing. However, giving people the opportunity to “research” subjects they know nothing about by consulting sources who have no need to be unbiased is not liberating. It is the exact opposite!

So what strategies are OK to use to persuade parents that vaccines are not only safe (relatively) but essential, rather than a tool of state control?

The argument that, without widespread vaccination, herd immunity cannot protect the few who cannot be vaccinated has been used. The counter argument is that parents see this as putting their child at risk to protect the greater good – as Mr Spock once said “the needs of the many outweigh the needs of the few, or the one.”

Even the argument that the main beneficiary of vaccination is the child themselves can be disputed as a biased statement produced by corrupt medical big business.

So is it time for a hard line approach?

Several have already been tried, from refusing access to schools, to removal of state benefit payments. However, parents who decide not to vaccinate are often relatively well off so these don’t always carry the bite they may otherwise do.

Many organisations are keen to support patents’ right to ethical and religious freedom against such draconian measures. Unsurprisingly, many lawyers are also keen to help uphold choice, for the right price. This does not mean the anti-vaccination movement is winning.

Some physicians in the US are even withholding healthcare provision unless a child is properly vaccinated.

Unfortunately, all of these measures seem to have one principle victim – the child themselves. The poor kid is already far more likely to get a potentially fatal, preventable diseases, now they won’t get proper schooling or medical care.

You’ll never forget the look of shock and betrayal that your tiny, innocent and trusting child gives you after the doctor jabs them with a needle for the first time – but I’d argue, it’s just part of growing up (yours not theirs).

Statistical analysis of over 5,000 published trials has highlighted 90 that contain dubious data.

This is equivalent to around 2% of the trials examined using statistical tools to identify anomalies hidden within the data. The authors of the study into anaesthesia trials point out that there could be many reasons for these anomalies – such as poor trial methodology, but clearly fraud is a possibility too.

All of these trials had been published in prestigious journals, including: Anaesthesia; Anaesthesia and Analgesia; European Journal of Anaesthesiology; Journal of the American Medical Association; and the New England Journal of Medicine.

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John Carlisle, a consultant anaesthetist at Torbay Hospital, carried out the analysis. He had previously used similar statistical tools to discover a high profile case of scientific fraud involving a Japanese anaesthesiologist who was found to have repeatedly fabricated data.

The tool works by comparing the baseline data, such as the height, sex, weight and blood pressure of trial participants, to known distributions of these variables in a random sample of the populations. This is a test hyperlink

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Carlisle reviewed data from 5,087 clinical trials published during the past 15 years. He concluded that 90 published trials had underlying statistical patterns that were unlikely to appear by chance in a credible dataset.

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“For 50 years, WWF has been protecting the future of nature. The world’s leading conservation organization, WWF works in 100 countries and is supported by 1.2 million members in the United States and close to 5 million globally.”

Kanye West, Producer.

The data in 43 of the trials had only about a one in a quadrillion chance of having occurred by chance.

I wonder how long it will be before a statistical tool is developed to massage falsified data so it is harder to detect?
Not that I’m a pessimist of course…

A recent report published by Doctors Without Borders titled ‘Lives on the edge’ analyses the failure of the current R&D system and goes on to outline new ways of developing tools to better address the medical needs of people at affordable prices. World governments have been urged to be proactive in the development of desperately needed new vaccines, diagnostics and medicines at affordable prices.

Doctors Without Borders is an independent international medical humanitarian organisation working to bring emergency medical care to people caught in conflict, crises, and disasters in more than 65 countries world over.

“People in poor and wealthy countries are now finding that the medicines they need either don’t exist or are priced so high that they can’t afford them, and governments need to solve these problems,” says an official of Doctors Without Borders in the report.

The report goes on to say pharmaceutical corporations woefully under-invest in research for diseases that aren’t lucrative, while governments have failed to ensure that taxpayer-funded research addresses priority health needs.

One example of this world wide crisis is in Zimbabwe, where their pharmaceutical sector is only producing eight percent of the country’s drugs, a startling indication that the country’s pharmaceutical industry is in crisis, a situation that puts their citizens under threat. Health is a sensitive topic all over the world, but for countries like Zimbabwe it is important to be able to produce the medicines necessary to provide for its people.

Most drug manufacturers in the country have closed shop because of the macro-economic environment, and the few that are left face stiff competition from cheap imports. Some of the companies that are either facing viability challenges or have closed shop include CAPS Holdings, MedTech Holdings, Wallace Laboratories, Lancaster Industries, and Reckitt and Benckiser.

The government, however, insists it is committed to promoting and encouraging the most cost effective local production of safe, high quality medicines at affordable prices.

The National Medical Device Curriculum is a set of four fictitious case studies intended to help academic institutions
and medtech companies understand US FDA’s medical device regulatory processes. The FDA believes that better understanding
of regulatory processes will accelerate the delivery of innovative medical devices to patients.

To understand the “substantial equivalence” decision-making process for a 510(k) submission.

To examine the 510(k) submission processes as a whole.

To prepare a traditional 510(k) (a write-up of key sections of a submission) in a team project.

To me, the 70s soap opera style jars but there is no doubt that the information is clear and well laid out – if you have
the recommended three hours to spend going each one. The following excerpt from case study one gives you a flavour…

“…And we’ll need to make sure the postmarket surveillance controls are in place, like medical device Reporting, which
includes tracking of adverse events. Then we go to market with your device!”

Neyhard held up one hand.
“Stop right there.”

Mooney and Laws shifted nervously in their seats. What had they missed?

To be continued…

Whitehall Trainings’ course,
Device Safety & Vigilance, was written by Steve Jolley – a Cambridge University graduate with 25 years’ experience
in drug & device safety & vigilance, who specializes in global safety compliance, business process improvement
and signal detection. He is the Chairperson of the DIA Clinical Safety and Pharmacovigilance steering committee for
North America and has worked with over 80 clients in the US, Europe and Japan. He is a featured speaker with the
FDA and MHRA at DIA conferences and webinars on drug safety topics including auditing and signalling).

Safety testing of drugs can be a contentious issue – testing of non-pharmaceuticals is even more so. Opinions are especially polarised where the test systems are live animals. Understandably, such practices are tightly controlled, and this is where Good Laboratory Practice plays a vital role.

In 1976, the FDA issued the first draft of the regulations that would become known as GLP. This was largely prompted by alarming findings at a US testing lab that, at the time, carried out almost half of the world’s toxicology tests. The OECD GLP principles came a little later and form the bedrock of toxicology and environmental studies, having been passed into the legislation of many countries.

The OECD defines GLP as “…a quality system concerned with the organisational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.” The principles are wide ranging – as the work covered varies enormously from those involving chemical tests carried out in a lab to large-scale field trials.

Whitehall Training has just published an online training course that deals with each of the following important aspects:

The History & Purpose of GLP – how the GLP principles were produced and the key role they play…

Test Facility Organisation & Personnel – organisational processes required, and how the GLP requirements for the responsibilities of various staff can be delivered in practice…

Quality Assurance – how SOPs, the study plan and master schedule are used to provide an independent audit function…

Like all of Whitehall’s training, the GLP course has a multiple-choice exam and a uniquely-numbered, named and dated certificate that can be used to demonstrate training compliance at audit. It has also been accredited with 6 CPD points by The Faculty of Pharmaceutical Medicine of the Royal College of Physicians of the United Kingdom.

About the author…

Roger Chapman is an internationally recognised expert in the interpretation and application of OECD Good Laboratory Practice to the full spectrum of regulatory studies, both in the laboratory and in the field. He also has extensive experience of Good Clinical Practice in the laboratory (GCLP), and Good Manufacturing Practice in the Quality Control laboratory environment.

A long-serving former Senior Quality Assurance Manager in the Contract Research industry, Roger has developed a tremendous depth of experience in compliance problem-solving. He has also led or participated in over 70 regulatory inspections from the MHRA, FDA and EPA, and has developed and maintained GxP quality systems and audit programmes for over 30 years.

Roger is a regular speaker at regional, national and international conferences and an established trainer/facilitator on professional development courses covering Quality, Compliance and Quality Assurance.